Multiple Sclerosis Progression and Relapse Activity in Children
Authors: Pietro Iaffaldano, Emilio Portaccio, Giuseppe Lucisano, Marta Simone, Alessia Manni, Tommaso Guerra, Damiano Paolicelli, Matteo Betti, Ermelinda De Meo, Luisa Pastò, Lorenzo Razzolini, Maria A. Rocca, Laura Ferrè, Vincenzo Brescia Morra, Francesco Patti, Mauro Zaffaroni, Claudio Gasperini, Giovanna De Luca, Diana Ferraro, Franco Granella, Carlo Pozzilli, Silvia Romano, Paolo Gallo, Roberto Bergamaschi, Maria Gabriella Coniglio, Giacomo Lus, Marika Vianello, Paola Banfi, Alessandra Lugaresi, Rocco Totaro, Daniele Spitaleri, Eleonora Cocco, Franco Di Palma, Davide Maimone, Paola Valentino, Valentina Torri Clerici, Alessandra Protti, Giorgia Teresa Maniscalco, Giuseppe Salemi, Ilaria Pesci, Umberto Aguglia, Vito Lepore, Massimo Filippi, Maria Trojano, Maria Pia Amato, Elisabetta Ferraro, Francesco O. Logullo, Girolama A. Marfia, Roberto Bombardi, Davide Nasuelli, Paolo Bellantonio, Milena De Riz, Paola Gazzola, Guido Cavaletti, Matilde Inglese, Antonella Conte, Gioacchino Tedeschi, Alessia Di Sapio, Alessandro Leone, Sara Montepietra, Bruno Marini, Maurizia Gatto, Maria Sessa, Maria T. Ferrò, Augusto Rini, Daniela Cargnelutti, Massimiliano Mirabella, Alessandro Burlina, Carlo Avolio, Paola Cavalla, Marco Rovaris, Bonaventura Ardito, Carlo Piantadosi, Paolo A. Confalonieri, Raffaella Clerici, Silvia Strumia, Francesca De Robertis, Rocco Quatrale, Leonardo Sinisi, Cristina Fioretti, Vincenzo Di Lazzaro, Sebastiano Bucello, Luca Mancinelli, Giuseppe Ribizzi, Roberto Zarbo, Luigi M. E. Grimaldi, Francesco Corea, Vincenzo Sidoti, Luca Massacesi, Roberto Balgera, Marcello C. Romano, Francesco D'Andrea, Anna Luisa Ancona, Matteo Pizzorno, Steno Rinalduzzi, Francesco Passantino, Lorenzo Capone, Marta Bianchi, Simonetta Venturi, Giuseppe Trivelli, Giampaolo Brichetto, Silvia Fermi, Placido Bramanti, Rosa Iodice, Maria Luisa Piras, Maria Grazia Celani, Paolo Barone, Tiziana Tassinari, Annamaria Marson, Marinella Clerico, Paola Banfi, Claudio Solaro
Journal: JAMA Neurology (2023)

Importance Although up to 20% of patients with multiple sclerosis (MS) experience onset before 18 years of age, it has been suggested that people with pediatric-onset MS (POMS) are protected against disability because of greater capacity for repair. Objective To assess the incidence of and factors associated with progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW) in POMS compared with typical adult-onset MS (AOMS) and late-onset MS (LOMS). Design, Setting, and Participants This cohort study on prospectively acquired data from the Italian MS Register was performed from June 1, 2000, to September 30, 2021. At the time of data extraction, longitudinal data from 73 564 patients from 120 MS centers were available in the register. Main Outcomes and Measures The main outcomes included age-related cumulative incidence and adjusted hazard ratios (HRs) for PIRA and RAW and associated factors. Exposures Clinical and magnetic resonance imaging features, time receiving disease-modifying therapy (DMT), and time to first DMT. Results After applying the inclusion and exclusion criteria, the study assessed 16 130 patients with MS (median [IQR] age at onset, 28.7 [22.8-36.2 years]; 68.3% female). Compared with AOMS and LOMS, patients with POMS had less disability, exhibited more active disease, and were exposed to DMT for a longer period. A first 48-week-confirmed PIRA occurred in 7176 patients (44.5%): 558 patients with POMS (40.4%), 6258 patients with AOMS (44.3%), and 360 patients with LOMS (56.8%) ( P &amp;amp;lt; .001). Factors associated with PIRA were older age at onset (AOMS vs POMS HR, 1.42; 95% CI, 1.30-1.55; LOMS vs POMS HR, 2.98; 95% CI, 2.60-3.41; P &amp;amp;lt; .001), longer disease duration (HR, 1.04; 95% CI, 1.04-1.05; P &amp;amp;lt; .001), and shorter DMT exposure (HR, 0.69; 95% CI, 0.64-0.74; P &amp;amp;lt; .001). The incidence of PIRA was 1.3% at 20 years of age, but it rapidly increased approximately 7 times between 21 and 30 years of age (9.0%) and nearly doubled for each age decade from 40 to 70 years (21.6% at 40 years, 39.0% at 50 years, 61.0% at 60 years, and 78.7% at 70 years). The cumulative incidence of RAW events followed a similar trend from 20 to 60 years (0.5% at 20 years, 3.5% at 30 years, 7.8% at 40 years, 14.4% at 50 years, and 24.1% at 60 years); no further increase was found at 70 years (27.7%). Delayed DMT initiation was associated with higher risk of PIRA (HR, 1.16; 95% CI, 1.00-1.34; P = .04) and RAW (HR, 1.75; 95% CI, 1.28-2.39; P = .001). Conclusions and Relevance PIRA can occur at any age, and although pediatric onset is not fully protective against progression, this study’s findings suggest that patients with pediatric onset are less likely to exhibit PIRA over a decade of follow-up. However, these data also reinforce the benefit for DMT initiation in patients with POMS, as treatment was associated with reduced occurrence of both PIRA and RAW regardless of age at onset.